pandemic. The number of adults with congenital heart disease (ACHD) with atrial fibrillation (AF) is expected to increase. We sought to assess the impact of AF on survival in Korean ACHD. Records of AF in ACHD were extracted from the records of the Korea National Health Insurance Service from 2006 through 2015. Multiple Cox proportional hazards analyses were carried out after adjustment for age, sex, income level, AF, and comorbidities. Survival rates (SRs) with and without AF were compared. The death records from 2006 through 2016 were included. A total of 3,999 ACHD had AF (51.4% were male) and 62,691 ACHD did not have AF (43.5% were male); the proportion of ACHD who were 60 years and older was 53.0% and 27.0% in those with and without AF, respectively ( < 0.001). The age-standardized incidence rate for AF was 1,842.0 persons per 100,000 people in the Korean general population from 2006 through 2015. For AF in ACHD, it was 5,996.4 persons per 100,000 ACHD during the same period, which was higher than that in the general population ( < 0.001). Significantly higher proportion of death (20.9%) occurred in ACHD with AF than without AF (8.3%) ( < 0.001). The adjusted hazard ratio for AF of death in ACHD was 1.39 (95% confidence interval, 1.29-1.50). The ten-year SR of ACHD with AF was 69.7% whereas it was 87.5% in non-AF ( < 0.001). In ACHD, AF occurs more frequently and has a worse prognosis than seen in the non-valvular general population in Korea. AF is associated with increased death in ACHD, especially with aging. In ACHD, AF occurs more frequently and has a worse prognosis than seen in the non-valvular general population in Korea. AF is associated with increased death in ACHD, especially with aging. Pregnant women are at a high-risk of influenza infection. We have previously reported a low influenza vaccination coverage rate (4.0%) in Korea during the 2006-2007 influenza season. We conducted follow-up studies in 2011-2012 and 2018-2019 to observe changes in influenza vaccination coverage. Women who delivered at Inha University Hospital (Incheon, Korea) in 2011-2012 and 2018-2019 were enrolled in the study. We surveyed the rate of influenza vaccination, perception scores, and related factors through telephonic interviews and compared the results from 2011-2012 and 2018-2019 with those from 2006-2007. The number of survey respondents was 227 in 2006-2007, 152 in 2011-2012, and 171 in 2018-2019. The rate of vaccination coverage increased from 4.0% in 2006-2007 to 42.0% in 2011-2012 and 59.3% in 2018-2019. Perception scores also increased progressively from 3.8 in 2006-2007 to 4.2 in 2011-2012 and 5.1 in 2018-2019. Physician recommendations for influenza vaccination also increased from 4.8% in 2006-2007 to 36.8% in 2011-2012 and 49.7% in 2018-2019. The most common reason for not getting vaccinated was the lack of awareness of influenza vaccination during pregnancy (36.9%). The perception scores and physician recommendation rates were significantly lower for unvaccinated women (3.87 and 8.4%, respectively) than for vaccinated women (5.14 and 69.1%, respectively). The influenza vaccination coverage rate in pregnant women has increased significantly since our study in 2006-2007. However, further improvement in the coverage rate is needed. There is a need for active and comprehensive publicity and education regarding this issue among physicians and pregnant women. The influenza vaccination coverage rate in pregnant women has increased significantly since our study in 2006-2007. However, further improvement in the coverage rate is needed. There is a need for active and comprehensive publicity and education regarding this issue among physicians and pregnant women.Infographics are pictorial representations of information intended to disseminate information quickly and clearly. Their use has increased in the past decade due to wider and easy access to technology. Infographics are being increasingly used for public advisories, disseminating protocols for healthcare professionals, and post-publication promotion of research. Due to their potential to rapidly reach a vast audience, these have gained larger importance during the coronavirus disease 2019 pandemic. Two key aspects determine the quality of infographics, content and visual appeal. In this brief, the authors attempt to delineate the key aspects of designing an infographic, and the freeware that they may have at their disposal for creating informative, appealing, and useful infographics. Early trauma is known to be a risk factor of suicide-related behavior. On the other hand, people who attempt suicide using a fatal method are reported to be more likely to complete suicide. https://www.selleckchem.com/Bcl-2.html In this study, we assumed that early trauma affects an individual's temperament and character and thereby increases the risk of a fatal method of suicide attempts. We analyzed 92 people with a history of previous suicide attempts. We compared the Temperament and Character Inventory-Revised scores between the groups with and without early trauma, and between the groups with and without a history of suicide attempt using fatal methods through an analysis of covariance with age, sex, and presence of a psychiatric history as covariates. A mediation analysis was conducted of the relationship between early trauma and fatal methods of suicide attempt with self-transcendence as a mediator. Higher self-transcendence was reported in the fatal group (27.71 ± 13.78 vs. 20.97 ± 12.27, = 0.010) and the early trauma group (28.05 ± 14.30 vs. 19.43 ± 10.73, = 0.001), respectively. The mediation model showed that self-transcendence mediates the relationship between early trauma and fatal methods of suicide attempt. The 95% confidence intervals for the direct and indirect effect were (-0.559, 1.390) and (0.026, 0.947), respectively. Self-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk. Self-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk.

Direct acting antivirals (DAAs) have revolutionized management of hepatitis C virus (HCV), but treatment uptake remains low among persons who inject drugs (PWID). We report the continuum of care for HCV and describe predictors of treatment with DAAs among PWID in Seattle. We analyzed data from the 2018 Seattle area National HIV Behavioral Surveillance (NHBS) survey of PWID. Persons ≥18 years of age who injected drugs in the past year and completed the core NHBS survey, a local survey supplement, and rapid HCV antibody testing were included. Among those who screened HCV antibody positive, we calculated proportions and 95 % confidence intervals for self-reported steps along the HCV care continuum. Multivariable logistic regression was used to calculate the adjusted odds (AOR) of having received DAA therapy. The sample included 533 PWID, 376 (71 %) of whom tested positive for antibodies to HCV. Among those who were HCV antibody positive, 94 % reported any prior HCV test, 81 % reported a prior confirmatory test, and 68 % reported a prior HCV diagnosis. Of those diagnosed, 26 % had undergone treatment and 18 % had been cured. In a multivariate model, being one year older (AOR 1.05 per year, 1.01-1.08) was predictive of DAA treatment, while homelessness (AOR 0.39, 0.19-0.80) and female gender (AOR 0.36, 0.16-0.78) were associated with a lower odds of DAA therapy. Despite widespread HCV testing among PWID in Seattle, treatment uptake remains low in the DAA era. In particular, treatment of women, younger adults and persons living homeless is lagging behind. Despite widespread HCV testing among PWID in Seattle, treatment uptake remains low in the DAA era. In particular, treatment of women, younger adults and persons living homeless is lagging behind. Exercise is increasingly being used in the treatment of alcohol use disorder (AUD). We examined the short-term effects of acute exercise on alcohol craving, mood states and state anxiety in physically inactive, non-treatment seeking adults with AUD. Exploratory, single-arm study. In total, 140 adults with AUD (53.7 ± 11.8 years; 70 % female) were included in a randomized controlled trial (RCT) to study effects of physical activity on alcohol consumption. This acute exercise study was nested within the larger RCT. The intervention was a 12-minute sub-maximal fitness test performed on a cycle ergometer. Participants self-rated their desire for alcohol (DAQ) and completed mood (POMS-Brief) and state anxiety (STAI-Y1) questionnaires 30-minutes before exercise, immediately before, immediately after, and 30-minutes post. Ratings of perceived exertion (RPE) were collected. Effects of exercise were assessed using RM-ANOVA and dependent sample t-tests with effect sizes (Hedges g). In total, 70.6 % had mild or moderate AUD (DSM-5 criteria = 4.9 ± 2). The intervention was generally perceived as 'strenuous' (RPE = 16.1 ± 1.6). In the total sample, there was a main effect of time with reductions in alcohol craving [F(3,411) = 27.33, p < 0.001], mood disturbance [F(3,411) = 53.44, p < 0.001], and state anxiety [F(3,411) = 3.83, p = 0.013]. https://www.selleckchem.com/TGF-beta.html Between-group analyses indicated larger magnitude effects in those with severe compared to mild AUD, however, AUD severity did not significantly moderate the within-group improvements group x time interaction for alcohol craving [F(6,411) = 1.21, p = 0.305]. Positive effects of exercise were maintained 30-minutes post-exercise. A short bout of aerobic exercise reduced alcohol craving and improved mood states in adults with AUD. A short bout of aerobic exercise reduced alcohol craving and improved mood states in adults with AUD. Illegally manufactured potent synthetic opioids (IMPSO) like fentanyl have contributed to rises in overdose deaths in parts of North America and Europe. While many of these substances are produced in Asia, there is little evidence they have entered markets there. We consider the susceptibility to IMPSO's encroachment in markets in the Asia-Pacific region. Our analysis focuses on Australia, China, India, and Myanmar. Using a mixed-methods approach comprising interviews, literature review, and secondary data analyses, we examine factors facilitating or impeding incursion of IMPSO. Finally, we illustrate the potential for IMPSO fatalities in Australia. Australia reports some signs of three facilitating factors to IMPSO's emergence 1) existing illicit opioid markets, 2) disruption of opioid supply, and 3) user preferences. The other three countries report only existing illicit opioid markets. While diverted pharmaceutical opioids are a noted problem in Australia and India, heroin is the dominant opioid in all four countries. There are divergent trends in heroin use, with use declining in China, increasing in India, and stable in Australia and Myanmar. If IMPSO diffused in Australia as in North America from 2014 to 2018, and our assumptions generally hold, deaths from IMPSO could range from 1500-5700 over a five-year period. This analysis and illustrative calculations serve as an early indication for policymakers. With the exception of Australia, many countries in the region fail to properly record overdose deaths or monitor changes in local drug markets. Early assessment and monitoring can give officials a better understanding of these changing threats. This analysis and illustrative calculations serve as an early indication for policymakers. With the exception of Australia, many countries in the region fail to properly record overdose deaths or monitor changes in local drug markets. Early assessment and monitoring can give officials a better understanding of these changing threats.Progesterone receptor (PR) antagonists have been found to be effective for treating certain human cancers. However, the steroidal structure of PR antagonists could bind to other hormone receptors, thus leading to serious side effects. On the other hand, non-steroidal PR antagonists have rarely been evaluated for their anti-cancer efficacy. Therefore, identifying novel non-steroidal PR antagonists possessing potent anti-cancer efficacy would be an attractive project to pursue. In this study, we presented a new metal-free oxidative CH arylation method to rapidly synthesize a series of 6-aryl-6H-benzo[c]chromene derivatives. Multiple cancer cell lines were used for their anti-cancer activity screening. An extensive analysis of structure-activity relationships (SAR) of the derivatives revealed that compounds 32 and 34 markedly inhibited the proliferation of MCF-7 cells with IC50 values of 6.32 ± 0.52 μM and 5.71 ± 0.49 μM, respectively. Further investigation indicated that derivatives 32 and 34 could elevate the expression of p21 and decrease the expressions of CDK4 and cyclin D1, leading to cell cycle arrest at G0/G1 phase.

No differences in microhardness indicated similar bone quality at the tissue level between the mutant and wildtype bones. Procollagen 1 N-terminal propeptide and osteocalcin were elevated in serum, and osteoblast number per bone perimeter and osteoid width per bone perimeter were elevated in tibias from the mutant mice. In contrast to mutations that constitutively activate GC-B, we report that mutations that enhance GC-B activity only in the presence of its natural ligand, increase bone mass, bone strength, and the number of active osteoblasts at the bone surface. Lipid mediators such as eicosanoids maintain various physiological processes, and their alterations are involved in the development of numerous cardiovascular diseases. https://www.selleckchem.com/products/1-phenyl-2-thiourea.html Therefore, the reliable assessment of their profile could be helpful in diagnosis as well as in eicosanoid biomarker-based treatment. Hence, the presented study aimed to develop and validate a new rapid, specific and sensitive LC-MS/MS method for quantification of arachidonic acid-derived eicosanoids in plasma, including lipid mediators generated via COX-, LOX- and CYP450-dependent pathways. The developed method features high sensitivity because the lower limit of quantification ranged from 0.05 to 0.50 ng mL-1 as well as the accuracy and precision estimated within 88.88-111.25% and 1.03-11.82%, respectively. An application of a simple and fast liquid-liquid extraction procedure for sample cleaning resulted in a highly satisfactory recovery of the analytes (>88.30%). Additionally, the method was validated using artificial plasma, an approach that enabled the elimination of the matrix effect caused by an endogenous concentration of studied lipid mediators. Importantly, the presented LC-MS/MS method allowed for simultaneous quantitative and qualitative [quan/qual] analysis of the selected eicosanoids, leading to an additional improvement of the method specificity. Moreover, the validated method was successfully applied for eicosanoid profiling in rat, mouse and human plasma samples, clearly demonstrating the heterogeneity of the profile of studied lipid mediators in those species. β-Lactams are the most widely used antibiotics in treating bacterial infections. However, they are rarely applied in infections caused by Vibrio parahaemolyticus, as the bacterium is intrinsically resistant to penicillins by expressing β-lactamase. Here we report structural characterization of the CARB β-lactamase from V. parahaemolyticus (CARB-20). CARB-20 is a class A β-lactamase, belonging to subclass A1 (containing 70STFKAL75, 130SDNTAANL137, 164RXEXXLN170, 231VGDKTG236, etc.), group LSBL2 (with the disulfide bridge C77-C123, motif 231IADRSGAG238 and R244). CARB-20 adopts a typical subclass A1 β-lactamase fold consisting of two domains. Its active site is constituted by four conserved motifs, similar to that of known subclass A1 β-lactamases. Analysis of the active site structure reveals its substrate preference for penicillin, ampicillin and carbenicillin but not for latterly developed cephalosporins. Meanwhile, β-lactamase inhibitors such as clavulanate and sulbactam can well fit into the active site, supporting β-lactams combined with β-lactamase inhibitors as a potential approach for treating infection of V. parahaemolyticus. The residues around the active site show certain variations, which can be useful for specific inhibitor design. In the directed evolution experiment, CARB-20 exhibited plasticity in developing significant resistance to inhibitors by accumulated residue substitutions. Therefore, careful monitoring of enzyme mutations is necessary for successfully applying β-lactam/β-lactamase inhibitor combination therapy. Taken together, our results open up an avenue of inhibitor design targeting vibrio β-lactamases, facilitating the application of β-lactams in treating vibrio infections. The promotion of senescence in cancer cells by dietary (poly)phenols gained attention as a promising chemopreventive strategy against colorectal (CRC) and other cancers. Urolithins (Uros) are ellagitannins and ellagic acid-derived gut microbiota metabolites that reach high concentrations in the human colon. They were postulated to be as potential anticancer agents in different CRC models, but their role as promoters of cellular senescence has never been comprehensively evaluated. We evaluated long-term senescent-mediated chemoprevention of physiologically relevant doses of different Uros and representative mixtures of human urolithin metabotypes in human CRC (HCT-116, Caco-2, and HT-29) and non-tumorigenic (CCD18-Co) cell lines. Our results show that Uro-A (but not Uro-C, IsoUro-A, or Uro-B) leads to a dose-dependent anti-clonogenic effect through the increase of the senescence-associated β-galactosidase activity, rather than by reversible cell cycle arrest and(or) apoptosis which require much higher concentrations. Senescence was accompanied by an elevated p53 and p21Cip1/Waf1 expression in HCT-116 cells (p53-wild type), but not in other CRC lines with p53 mutated or non-tumorigenic cells, which suggests that long-term senescence-mediated chemoprevention is a p53-dependent manner. Moreover, the ATP-binding cassette transporters and the phase-II metabolism of Uros limited the induction of senescence, which anticipates lower effects of conjugated Uros against systemic cancers. Conventional toxicological risk assessment methods mainly working on single chemicals that fail to adequately address the simultaneous exposure and their potential toxicity in humans. We herein investigated the toxic heavy metals lead (Pb), arsenic (As), and methylmercury (MeHg) and their binary mixtures role in neurodegenerative diseases. To characterize the toxicity of metal mixtures at the molecular level, we established a non-animal omics-based organ relevant cell model system. The obtained experimental data was refined by using the statistical and downstream functional analysis. The protein expression information substantiates the previous findings of single metal (Pb, As, and MeHg) induced alterations to mitochondrial dysfunction, oxidative stress, mRNA splicing, and ubiquitin system dysfunction relation to neurodegenerative diseases. The functional downstream analysis of single and binary mixtures protein data is presented in a comparative manner. The heavy metals mixtures' outcome showed significant differences in the protein expression compared to single metals that indicate metal mixtures exposure is more hazardous than single metal exposure.

RESULTS ERFD, CVI, and AVCF were all significant predictors of elbow injury risk after accounting for pitcher age, weight, and workload. The analysis identified 3 specific indicators of heightened risk based on the results of a CMJ scan low ERFD, a combination of low AVCF and high CVI, and a combination of high AVCF and low CVI. In contrast, shoulder injury risk was roughly independent of all 3 CMJ test measurements. CONCLUSION This study supports the hypothesis of the entire kinetic chain's involvement in pitching by establishing a link between CMJ test performance and elbow injury risk in professional baseball pitchers. CMJ assessment may be a powerful addition to injury risk alert and prevention protocols. Pitchers in high-risk groups can be prescribed specific exercise plans to improve movement imbalances.BACKGROUND Patients who undergo hip arthroscopy inevitably experience pain postoperatively; however, the efficacy and safety of adjunct analgesia to prevent or reduce pain are not well-understood. https://www.selleckchem.com/products/poly-l-lysine.html PURPOSE To perform a comprehensive qualitative synthesis of available randomized controlled trials evaluating the effect of adjunct analgesia on postoperative (1) pain, (2) opioid use, and (3) length of stay (LOS) in patients undergoing hip arthroscopy. STUDY DESIGN Systematic review. METHODS PubMed, OVID/MEDLINE, and Cochrane Controlled Register of Trials were queried for studies pertaining to analgesia interventions for patients undergoing hip arthroscopy. Two authors independently assessed article bias and eligibility. Data pertaining to changes in pain scores, additional analgesia requirements, length of hospital stay, and complications were extracted and qualitatively reported. Network meta-analyses were constructed to depict mean pain, opioid use, and LOS among the 3 analgesia categories (blocks, local infiltrconclusive evidence that it reduces length of hospital stay. Furthermore, it appears that local infiltration analgesia may provide the greatest benefits in reductions in pain and opioid consumption. We recommend the use of adjunct analgesia in appropriately selected patients undergoing hip arthroscopy without contraindication who are at a high risk of severe postoperative pain.Simultaneous analysis based on encoded fluorophores suffers from potential crosstalk between fluorophores and the limited number of colors that can be practically resolved. Inspired by nontrivial temporal patterns in living organisms, we developed a DNA-templated probe by utilizing DNA polymerase (DNAP) for multiplexed detection of nucleic acids. These probes use differential delay times of signaling by a DNAP-mediated extension to distinguish different targets, which serve as the primers. Taking advantage of the high processivity and the controllable kinetics of DNAP, we find that multiplexed detection can be achieved in homogeneous solution using a single fluorophore. As a proof of concept, we developed assays for genomic DNA from four different bacteria. In addition, we designed and implemented probes to undergo a single oscillation in signal as an alternative way for multiplexing. We anticipate this approach will find broad applications not only in sensing but also in synthetic DNA nanosystems.The control of domain walls or spin textures is crucial for spintronic applications of antiferromagnets. Despite many efforts, it has been challenging to directly visualize antiferromagnetic domains or domain walls with nanoscale resolution, especially in magnetic field. Here, we report magnetic imaging of domain walls in several uniaxial antiferromagnets, the topological insulator MnBi2Te4 family, using cryogenic magnetic force microscopy (MFM). Our MFM results reveal higher magnetic susceptibility inside the domain walls than in domains. Domain walls in these antiferromagnets form randomly with strong thermal and magnetic field dependence. The direct visualization of these domain walls and domain structures in the magnetic field will not only facilitate the exploration of intrinsic topological phenomena in antiferromagnetic topological insulators but will also open a new path toward control and manipulation of domain walls or spin textures in functional antiferromagnets.In this study, a visible-light-induced intermolecular C-H bond imidation of arenes was achieved at ambient condition. By using simple phthalimide with (diacetoxyiodo)benzene and molecular iodine, direct metal-/photocatalyst-free C-N bond formation was achieved. The imidation protocol was designed by using time-dependent density functional theory calculations and experimentally demonstrated for 28 substrates with as high as 96% yield. Mechanistic studies indicated that radical-mediated aromatic substitution occurred via photolysis of N-iodophthalimide under visible-light irradiation.Phosphate ions perform a variety of functions in metabolic processes and are essential for all living organisms. The determination of the concentration of phosphate ions is useful in clinical diagnosis of various diseases as an inadequate phosphate level could lead to many health problems. In the search for a cost-effective method of fast monitoring, we investigated the use of cobalt ferrite nanoparticles (CoFeNPs) in the selective recognition of phosphate ions dissolved in aqueous media and more complex samples, such as human blood serum. We prepared these NPs by a chemical coprecipitation route and subjected them to annealing at 600 °C for 1 h. The successful formation of the NPs was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and hysteresis loop measurements. The NPs exhibited a ferrimagnetic behavior, a spinel-type crystalline structure, and hexagonal shape in the nanoscale range. We demonstrated that CoFeNPs containing immobilized fluorescent-labeled single-chain DNA (ssDNA*) probes can be applied for the fast selective detection of phosphate ions dissolved in a liquid medium. We have explored the fact that phosphate groups can displace ssDNA* probes attached to the nanoparticles, therefore causing a perceptible change in the fluorescence signal of the supernatant liquid. This detection method has been tested for the sensing of phosphate ions present both in aqueous solutions and in biological samples, with excellent selectivity and a low limit of detection (∼1.75 nM).

Ultrahigh molecular weight (UHMW) poly(ethylene oxide) (PEO) is a synthetic hydrophilic polymer with wide dispersity which shows considerable promise as a hemostatic agent in the treatment of gastrointestinal bleeding. Currently there is no analytical method for the determination of highly disperse UHMW PEO in biological samples that would allow its characterization in vivo and support its clinical development. Although liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful bioanalytical tool, it faces major challenges when applied to UHMW PEO. In this work, we report a novel bioanalytical method for the determination of UHMW PEO involving microsolid phase extraction (μ-SPE), chromatography on a PLRP-S 1000 Å reversed phase column and detection by positive ion Q-Q-TOF MS using the MSALL technique. In this mode, dissociation of all precursor ions in Q2 generated a series of product ions at m/z 89.0715, 133.0854, 177.1047, and 221.1475 of which the product ion at m/z 133.0854 was common to all precursor ions and enabled quantitation of all polymers in UHMW PEO. The method was successfully applied to the determination of UHMW PEO polymers in rat plasma, urine, and feces after oral administration of 1700 kDa PEO. The results show that UHMW PEO is not absorbed into the blood and is largely eliminated unchanged in feces over 48 h. We maintain the method is sufficiently robust to be used in routine bioanalysis of polymers with UHMW and wide dispersity.Studies of the topology, functioning, and regulation of metabolic systems are based on two main types of information that can be measured by mass spectrometry the (absolute or relative) concentration of metabolites and their isotope incorporation in 13C-labeling experiments. https://www.selleckchem.com/products/poly-l-lysine.html These data are currently obtained from two independent experiments because the 13C-labeled internal standard (IS) used to determine the concentration of a given metabolite overlaps the 13C-mass fractions from which its 13C-isotopologue distribution (CID) is quantified. Here, we developed a generic method with a dedicated processing workflow to obtain these two sets of information simultaneously in a unique sample collected from a single cultivation, thereby reducing by a factor of 2 both the number of cultivations to perform and the number of samples to collect, prepare, and analyze. The proposed approach is based on an IS labeled with other isotope(s) that can be resolved from the 13C-mass fractions of interest. As proof-of-principle, we analyzed amino acids using a doubly labeled 15N13C-cell extract as IS. Extensive evaluation of the proposed approach shows a similar accuracy and precision compared to state-of-the-art approaches. We demonstrate the value of this approach by investigating the dynamic response of amino acids metabolism in mammalian cells upon activation of the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), a key component of the unfolded protein response. Integration of metabolite concentrations and isotopic profiles reveals a reduced de novo biosynthesis of amino acids upon PERK activation. The proposed approach is generic and can be applied to other (micro)organisms, analytical platforms, isotopic tracers, or classes of metabolites.Co-substituted LaFeO3 was electrodeposited on the surface of BiVO4 as a co-catalyst to enhance the water splitting performance. Compared to bare BiVO4, the BiVO4/Co-LaFeO3 composite photoanode shows a water oxidation photocurrent of 3.4 mA/cm2 at 1.23 V versus reverse hydrogen electrode, accompanied by a notable cathodic shift in the onset potential for 300 mV. Combined optical and electrochemical characterizations show that the solid/electrolyte charge transfer efficiency of BiVO4 are dramatically improved by the incorporation of Co-substituted LaFeO3. From the surface kinetic study of charge carriers by intensity-modulated photocurrent spectroscopy, a suppressed surface recombination rate constant is observed and the enhanced photoelectrochemical water splitting performance observed in the BiVO4/Co-LaFeO3 photoanode is attributed to the surface passivation effect of Co-substituted LaFeO3.Mobility isolated spectra were obtained for protonated monomers of 42 volatile oxygen containing organic compounds at ambient pressure using a tandem ion mobility spectrometer with a reactive stage between drift regions. Fragment ions of protonated monomers of alcohols, acetates, aldehydes, ketones, and ethers were produced in the reactive stage using a 3.3 MHz symmetrical sinusoidal waveform with an amplitude of 1.4 kV and mobility analyzed in a 19 mm long drift region. The resultant field induced fragmentation (FIF) spectra included residual intensities for protonated monomers and fragment ions with characteristic drift times and peak intensities, associated with ion mass and chemical class. High efficiency of fragmentation was observed with single bond cleavage of alcohols and in six-member ring rearrangements of acetates. Fragmentation was not observed, or seen weakly, with aldehydes, ethers, and ketones due to their strained four-member ring transition states. Neural networks were trained to categorize spectra by chemical class and tested with FIF spectra of both familiar and unfamiliar compounds. Rates of categorization were class dependent with best performance for alcohols and acetates, moderate performance for ketones, and worst performance for ethers and aldehydes. Trends in the rates of categorization within a chemical family can be understood as steric influences on the energy of activation for ion fragmentation. Electric fields greater than 129 Td or new designs of reactive stages with improved efficiency of fragmentation will be needed to extend the practice of reactive stage tandem IMS to an expanded selection of volatile organic compounds.A wide range of collision cross section (CCS) databases for different families of compounds have recently been established from ion mobility mass spectrometry (IM-MS) measurements. Nevertheless, the need to validate these new data sets to provide the necessary confidence about the use of this parameter is increasingly expressed by the scientific community. If such a validation requires that complementary mass spectrometry experiments are conducted, it also appears that alternative strategies can contribute to the validation of such empirical data. In particular, in silico approaches are relevant to compute theoretical CCS values, to be compared to experimental ones. A recently published CCS database for 300 steroids allowed one to observe experimentally significant deviations of the expected CCS versus m/z correlations for some compounds. The present work attempts to rationalize such deviations with Density Functional Theory (DFT) calculations. MN15/6-311++G(d,p) investigations have been carried out, starting with a conformational analysis of a sample of 20 selected steroids and the determination of their preferred gas-phase ionization site.

J Res Proteome 161806-1816, 2017).OpenVax is a computational workflow for identifying somatic variants, predicting neoantigens, and selecting the contents of personalized cancer vaccines. It is a Dockerized end-to-end pipeline that takes as input raw tumor/normal sequencing data. It is currently used in three clinical trials (NCT02721043, NCT03223103, and NCT03359239). In this chapter, we describe how to install and use OpenVax, as well as how to interpret the generated results.Tumor neoantigens are at the core of immunological tumor control and response to immunotherapy. In silico prediction of tumor neoantigens from next-generation sequencing (NGS) data is possible but requires the assembly of complex, multistep computational pipelines and extensive data preprocessing. Using public data from two cancer cell lines, here we show how TIminer, a framework to perform immunogenomics analyses, can be easily used to assemble and run customized pipelines to predict cancer neoantigens from multisample NGS data.MHCflurry is an open source package for peptide/MHC I binding affinity prediction. Its command-line and programmatic interfaces make it well-suited for integration into high-throughput bioinformatic pipelines. Users can download models fit to publicly available data or train predictors on their own affinity measurements or mass spec datasets. This chapter gives a tutorial on essential MHCflurry functionality, including generating predictions, training new models, and using the MHCflurry Python interface. MHCflurry is available at https//github.com/openvax/mhcflurry .The plethora of RNA-seq data which have been generated in the recent years constitutes an attractive resource to investigate HLA variation and its relationship with normal and disease phenotypes, such as cancer. However, next generation sequencing (NGS) brings new challenges to HLA analysis because of the mapping bias introduced by aligning short reads originated from polymorphic genes to a single reference genome. Here we describe HLApers, a pipeline which adapts widely used tools for analysis of standard RNA-seq data to infer HLA genotypes and estimate expression. By generating reliable expression estimates for each HLA allele that an individual carries, HLApers allows a better understanding of the relationship between HLA alleles and phenotypes manifested by an individual.Nanopore sequencing, enabled initially by the MinION device from Oxford Nanopore Technologies (ONT), is the only technology that offers portable, single-molecule sequencing and ultralong reads. The technology is ideal for the typing of human leukocyte antigen (HLA) genes for transplantation and cancer immunotherapy. However, such applications have been hindered by the high error rate of nanopore sequencing reads. We developed the workflow and bioinformatic pipeline, Athlon (accurate typing of human leukocyte antigen by Oxford Nanopore), to perform high-resolution typing of Class I HLA genes by nanopore sequencing. The method features a novel algorithm for candidate allele selection, followed by error correction through consensus building. Here, we describe the protocol of using Athlon packaged in a VirtualBox image for the above application.The human leukocyte antigen (HLA) complex is necessary for antigen presentation and regulates both innate and adaptive immune responses. In the context of cancer and treatment therapies, the HLA locus plays a critical role in tumor recognition and tolerance mechanisms. In silico HLA class I and class II typing, as well as expression quantification from next-generation RNA sequencing, can therefore have great potential clinical applications. However, HLA typing from short-read data is a challenging task given the high polymorphism and homology at the HLA locus. https://www.selleckchem.com/products/abt-199.html In this chapter, we present our highly accurate HLA typing solution, arcasHLA. We provide a detailed outline for practitioners using our protocol to perform HLA typing and demonstrate the applicability of arcasHLA in several clinical samples from tumors.A standard strategy to discover somatic mutations in a cancer genome is to use next-generation sequencing (NGS) technologies to sequence the tumor tissue and its matched normal (commonly blood or adjacent normal tissue) for side-by-side comparison. However, when interrogating entire genomes (or even just the coding regions), the number of sequencing errors easily outnumbers the number of real somatic mutations by orders of magnitudes. Here, we describe SomaticSeq, which incorporates multiple somatic mutation detection algorithms and then uses machine learning to vastly improve the accuracy of the somatic mutation call sets.Identification of somatic mutations in tumor tissue is challenged by both technical artifacts, diverse somatic mutational processes, and genetic heterogeneity in the tumors. Indeed, recent independent benchmark studies have revealed low concordance between different somatic mutation callers. Here, we describe Somatic Mutation calling method using a Random Forest (SMuRF), a portable ensemble method that combines the predictions and auxiliary features from individual mutation callers using supervised machine learning. SMuRF has improved prediction accuracy for both somatic point mutations (single nucleotide variants; SNVs) and small insertions/deletions (indels) in cancer genomes and exomes. Here, we describe the method and provide a tutorial on the installation and application of SMuRF.Somatic variant callers identify mutations found within cancer genome sequencing data through mapping sequencing reads to a universal reference genome and inferring likelihoods from statistical models. False positives, however, are common among various tools as mismatches with the universal reference can also occur due to germline variants. Previous applications of personalized reference construction are not amenable with cancer genome analysis. Here, we describe an individualized approach for somatic variant discovery through the step-by-step usage of Personalized Reference Editor for Somatic Mutation discovery in cancer genomics (PRESM), a personalized reference editor for somatic mutation discovery in cancer genomes.

Polyphenolic compounds (including flavonoids, chalcones, phenolic acids, and furanocoumarins) represent a common part of our diet, but are also the active ingredients of several dietary supplements and/or medications. These compounds undergo extensive metabolism by human biotransformation enzymes and the microbial flora of the colon. CYP2D6 enzyme metabolizes approximately 25% of the drugs, some of which has narrow therapeutic window. Therefore, its inhibition can lead to the development of pharmacokinetic interactions and the disruption of drug therapy. In this study, the inhibitory effects of 17 plant-derived compounds and 19 colonic flavonoid metabolites on CYP2D6 were examined, employing two assays with different test substrates. The O-demethylation of dextromethorphan was tested employing CypExpress 2D6 kit coupled to HPLC analysis; while the O-demethylation of another CYP2D6 specific substrate (AMMC) was investigated in a plate reader assay with BioVision Fluorometric CYP2D6 kit. Interestingly, some compounds (e.g., bergamottin) inhibited both dextromethorphan and AMMC demethylation; however, certain substances proved to be inhibitors only in one of the assays applied. Our results demonstrate that some polyphenols and colonic metabolites are inhibitors of CYP2D6-catalyzed reactions. Nevertheless, the inhibitory effects showed strong substrate dependence. Bone cancer pain (BCP) remains a difficult clinical problem. This study examined whether pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is effective for attenuating BCP, and investigated the interaction between activation of PPARγ and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) / mammalian target of rapamycin (mTOR) signal in the spinal dorsal horn (SDH) of BCP rats. We tested the effects of intrathecal (i.t.) injection of adenovirus-mediated PTEN (Ad-PTEN), PTEN antisense oligonucleotide (Ad-antisense PTEN), mTOR inhibitor rapamycin, pioglitazone and PPARγ antagonist GW9662 on bone cancer-induced mechanical allodynia by measuring the paw withdrawal threshold (PWT). Western blot or immunofluorescence examined the expression of spinal PPARγ, PTEN, mTOR, p-mTOR and p-S6K1. Bone cancer did not alter total mTOR expression but caused significant downregulation of PTEN and upregulation of p-mTOR and p-S6K1 in spinal neurons. Rapamycin markedly reduced BCng the PPARγ/PTEN/mTOR signal in the SDH. Our data provided new insight in the therapeutic strategy in BCP management.Picroside I, a hepatoprotectant isolated from Picrorhiza kurroa Royle ex Benth and P. scrophulariiflora Pennell, can reduce liver injury in humans and animals. However, its anti-fibrosis effect remains elusive. This work aimed to explore the mechanism underlying the hepatoprotective effect of picroside I against hepatic fibrosis. Male mice (12 mice per group) were randomly divided into six groups the control group; the model group, which received thioacetamide (TAA); the positive group, which received TAA + S-(5'-adenosyl)-l-methionine (SAMe, 10 mg/kg); the low-dose group, which received TAA + picroside I (25 mg/kg); the middle-dose group, which received TAA + picroside I (50 mg/kg); and the high-dose group, which received TAA + picroside I (75 mg/kg). Serum biochemical indicators were detected, and histological evaluation was performed. Metabolomics and proteomic analyses were conducted via liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS). Data showed that picroside I could decrease the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), collagen type IV (CIV), N-terminal peptide of type III procollagen (PIIINP), laminin (LN), and hyaluronic acid (HA) and reduced fibrosis area. Picroside I altered metabolomic profiles, including energy, lipid, and glutathione (GSH) metabolism, in ice with fibrosis. Additionally, 25 differentially expressed proteins in the picroside I high-dose-treated group were reversed relative to in the model group. https://www.selleckchem.com/products/direct-red-80.html These proteins were involved in the sphingolipid signaling pathway, primary bile acid biosynthesis, and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Moreover, this study revealed how picroside I could protect against TAA-induced liver fibrosis in mice. Results indicated that picroside I can serve as a candidate drug for hepatic fibrosis.Hepatocellular carcinoma (HCC) is one of the most common cancers with the highest morbidity and mortality. It is necessary to develop new anti-liver cancer drugs. Itraconazole is a popular systemic anti-fungal drug with a strong anti-tumor effect. However, so far, it is not clear whether itraconazole has specific anti-tumor effect on liver cancer. The purpose of this study was to investigate itraconazole resistant effect of liver cancer and to explore its potential anti-cancer mechanism. The effect of itraconazole on the proliferation of liver cancer cells was studied with MTT assay. Flow cytometry was used to determine the effect of itraconazole on apoptosis, cell cycle distribution, changes in intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). In addition, after DAPI staining, nuclear morphological changes were observed under the fluorescent microscope, and the release of lactate dehydrogenase (LDH) was measured using the microplate reader. Finally, the expressions of proteins related to the anti-tumor signaling pathway were determined by Western blotting. The results showed that itraconazole significantly inhibited the proliferation of HepG2 and Bel-7405 cells. In addition, the data showed that itraconazole induced apoptosis in HepG2 cells, increased the production of ROS, blocked cell cycle, and decreased MMP. Furthermore, itraconazole inhibited HCC cell growth and promoted apoptosis through the Hh, Wnt/catenin, AKT/mTOR/S6K, ROS and death receptor pathways. Finally, we come to the conclusion that itraconazole exerts anti-liver cancer effect, and has potential for use as a new drug for liver cancer in clinic.Severe caloric-restriction compromises thyroid hormone (TH) status, apparently to save energy and proteins for enduring stress stimulus. However, a persistent decrease in TH levels may compromise heart function. We hypothesized that supplementation of low dose active TH or targeting hypoxia-inducible factor-1-alpha, HIF-1α (a strong activator of deiodinase enzyme that degrades peripheral active THs) will prevent deterioration of cardiac performance. Adult mice were subjected to acute fasting based on institutional animal protocols with ad libitum access to water. The following groups were studied Control mice with free access to food; severe caloric restriction fasting only group; Fasting with Triiodo-l-Thyronine (T3); Fasting with HIF-1α inhibitor (BAY). Cardiac hemodynamic and electrophysiological studies were performed and role of long noncoding RNAs were explored. Following severe caloric-restriction, we found that body weights, and heart weights to a partial extent, were decreased. Low-dose T3 treatment attenuated left ventricular hemodynamic impairment in indices of cardiac contractility and relaxation.

Our study demonstrated the safety and efficacy of FMT administered via retention enema, a simple bedside procedure, for the treatment and prevention of recurrent non-severe and severe CDI with an overall cure rate of 91%. Our study demonstrated the safety and efficacy of FMT administered via retention enema, a simple bedside procedure, for the treatment and prevention of recurrent non-severe and severe CDI with an overall cure rate of 91%.α motor neurons (MNs) are a target of the environmental neurotoxicant methylmercury (MeHg), accumulating MeHg and subsequently degenerating. In mouse spinal cord MN cultures, MeHg increased intracellular Ca2+ [Ca2+]i; the AMPA receptor (AMPAR) antagonist CNQX delayed the increase in [Ca2+]i, implicating the role of AMPARs in this response. Here we used human induced pluripotent stem cell-derived MNs (hiPSC-MNs), to characterize the role of MN AMPARs in MeHg neurotoxicity. Acute exposure to MeHg (0.1, 0.2, 0.5, 1 and 1.5 μM), fura-2 microfluorimetry, and a standard cytotoxicity assay, were used to examine MN regulation of [Ca2+]i, and cytotoxicity, respectively. Contribution of Ca2+-permeable and impermeable AMPARs was compared using either CNQX, or the Ca2+-permeable AMPAR antagonist N-acetyl spermine (NAS). MeHg-induced cytotoxicity was evaluated following a 24 h delay subsequent to 1 h exposure of hiPSC-MNs. MeHg caused a characteristic biphasic increase in [Ca2+]i, the onset of which was concentration-dependent; higher MeHg concentrations hastened onset of both phases. CNQX significantly delayed MeHg's effect on onset time of both phases. In contrast, NAS significantly delayed only the 2nd phase increase in fura-2 fluorescence. Exposure to MeHg for 1 h followed by a 24 h recovery period caused a concentration-dependent incidence of cell death. These results demonstrate for the first time that hiPSC-derived MNs are highly sensitive to effects of MeHg on [Ca2+]i, and cytotoxicity, and that both Ca2+-permeable and impermeable AMPARs contribute the elevations in [Ca2+]i.During a survey of the production of goniodomin A (GDA) by Alexandrium pseudogonyaulax in Danish coastal waters, Krock et al. (2018) obtained mass spectral evidence for the presence of a truncated congener, herein termed GD754, having a molecular weight 14 Da lower than GDA and assigned it as goniodomin B (GDB). An erroneous structure of GDB involving deletion of a methylene group between rings B and D had previously been reported by Espiña et al. (2016) but without experimental details. https://www.selleckchem.com/products/Cyclopamine.html HPLC properties reported by Krock for GD754 point to it being a homolog of GDA. Comparison of mass spectral fragmentation data reported for GD754 with fragmentation data for GDA, show it to be a truncated form of GDA with the deletion involving a CH2 group from ring F or one of the two methyl substituents on ring F, not elsewhere on the molecule. On biosynthetic grounds, the GD754 congener is proposed to be 34-desmethyl-GDA. Further experimental work will be required to confirm this hypothesis.Scorpion envenomations are a major public health problem in Brazil, and most medically important cases are attributable to the Tityus genus. The objective of this study is to describe the clinical and epidemiological aspects of a series of 151 cases of confirmed scorpion stings, which were treated at the hospitals of two cities in the Western Brazilian Amazon, between June 2014 and December 2019. This study shows that the genus Tityus was the most prevalent. Tityus (Atreus) metuendus (Pocock, 1897) was responsible for the greatest number of cases (68.2%), followed by Tityus (Archaeotityus) silvestris (Pocock, 1897) (14.6%). Most of the envenomations involved males (53.6%), and analysis showed a slight predominance in the group from 40 to 49 years (22.5%). The most affected body regions were feet (49.0%) and hands (31.8%). The time elapsed between the accident and medical care was ≤6 h in 92.1% of cases. Regarding clinical severity, classes I (80.8%) and II (15.9%) predominated. However, there were five (3.3%)ntivenoms have little effectiveness when used in the treatment of envenomations by some Amazonian scorpions.Many researchers have limited access to fully equipped laboratory-scale batch bioreactors and chemostats due to their relatively high cost. This becomes particularly prohibitive when multiple replicas of the same experiment are required, but not enough bioreactors are available to operate simultaneously. Additionally, experiments using shaken flasks are common but show significant limitations in terms of maintaining homogeneous conditions in liquid cultures or installing instrumentation for monitoring. Here, we proposed to tackle this significant hurdle by providing a route to make available the manufacture of low-cost, milliliter-scale bioreactors. This approach seems plausible for enabling proof-of-concept experiments before moving to a larger scale without significant investments. The conceptually designed systems were based on external-loop bioreactors due to their flexibility, simplicity, and ease of assembling and testing. Designs were initially evaluated in silico with the aid of COMSOL Multiphysics. The successfully evaluated systems were then constructed via additive manufacturing and assembled for hydrodynamics testing via tracer methods. This was enabled by a newly home-made optical absorbance sensor (OAS) for in-line and real-time measurements. Both the in silico and experimental results indicated close to ideal mixing conditions and low shear stress. Cell growth curves were prepared by culturing Escherichia coli and following its cell density in real-time. Our cell growth rate and maximum cell density were similar to those previously obtained in closely related systems. Therefore, the proposed bioreactors are an affordable alternative for batch and continuous cell growth studies rapidly and inexpensively.The identification of effective cognitive rehabilitation strategies for people with multiple sclerosis (MS) is critically important, as cognitive difficulties are prevalent in MS. Relatively few cognitive rehabilitation studies in MS have examined working memory (WM) training specifically, and the extent that WM training may impact neural activity on untrained tasks is not well understood. In the present study, we examined the effects of 20 sessions of adaptive WM training (using an n-back task with visually presented letter stimuli) on neural indices of the transfer of training gains to untrained tasks in MS and healthy control participants. Event-Related Potential (ERP) measures were obtained before (pretest) and after training (posttest) on untrained visual tasks of spatial WM (Spatial 3-back task), cognitive control (Go/Nogo Flanker task), and processing speed and selective attention (Search task). At posttest compared to pretest, MS and control groups exhibited enhancement of N1 amplitude for the Spatial 3-back; attenuation of P2 amplitude, and enhancement of N2 amplitude for the Go/NoGo Flanker task; and enhancement of P2 and N2 amplitude for the Search task.

The tunable perfect magnetic mirror effect and the retroreflector property may provide ways in novel photonic devices and sensing applications.Programmable multipurpose photonic integrated circuits require software routines to make use of their flexible operation as desired. https://www.selleckchem.com/products/crenolanib-cp-868596.html In this work, we propose and demonstrate the use of a modified tree-search algorithm to automatically determine the optimum optical path in a field-programmable photonic gate array (FPPGA), based on end-user specifications, circuit architecture and imperfections in the realized FPPGA arising, for example, from fabrication variations. In such a scenario, the proposed algorithm only requires the hardware topology and the location of the connections of the FPPGA defining the optical path to be programmed. The routine is able to optimize the path over multiple and competing objectives like the overall length, accumulated loss and power consumption. In addition, should any region of the circuit suffer from any potential damage that may affect the device performance, this algorithm is also able to provide basic self-healing and fault-tolerance capabilities by supplying alternative paths through the photonic arrangement.This paper presented a heterodyne speckle interferometer (HSI) for the measurement of two-dimensional in-plane displacement. A diffraction grating is used to split the light source into four beams, which are then reflected into a non-mirror measurement surface at symmetrical incident angles, before being scattered to form an interference pattern. In accordance with the Doppler Effect, in-plane displacement of the surface causes phase variations in speckle interference patterns, from which displacement information can be obtained. Several experiments were performed to evaluate the feasibility of the proposed HSI. Experiment results demonstrate that the proposed system is capable of accurately measuring in-plane displacement with a resolution of approximately 1.5 nm.Two diffractive optical elements are used to create a compact raster THz scanning setup in reflective configuration. The first one focuses the radiation into the small focal spot on the sample, while the second one collects reflected radiation and focuses it on the detector. To assure small size of the setup and large apertures of optical elements, structures work in the off-axis geometry. Thus, the focal spot is formed 100 mm after and 60 mm below the optical axis of the element, which measures 75 mm in diameter. The designed iterative algorithm allows further minimization of these values.Photonic topological transitions (PTTs) in metamaterials open up a novel approach to design a variety of high-performance optical devices and provide a flexible platform for manipulating light-matter interactions at nanoscale. Here, we present a wideband spectral-selective solar absorber based on multilayered hyperbolic metamaterial (HMM). Absorptivity of higher than 90% at normal incidence is supported over a wide wavelength range from 300 to 2215 nm, due to the topological change in the isofrequency surface (IFS). The operating bandwidth can be flexibly tailored by adjusting the thicknesses of the metal and dielectric layers. Moreover, the near-ideal absorption performance can be retained well at a wide angular range regardless of the incident light polarization. These features make the proposed design hold great promise for practical applications in energy harvesting.In this paper, we introduce a novel method for the fabrication of self-assembly plasmonic metamaterials by exploiting fluid instabilities of optical thin films. Due to interplay between template reflow and spinodal dewetting, two metal nanoparticles of different sizes are generated on the top mesas of free-standing porous anodic aluminum oxide (AAO) template, which results in the apprearance of double resonant peaks in the extinction spectrum. These two resonant peaks possess refractive index resolution 3.27 × 10-4 and 2.53 × 10-4 RIU, respectively. This optical intensity modulation based plasmonic nanoplatform shows a dramatically surface sensing performance with outstanding detection capacity of biomolecules, because of the very small decay length of electric field at dual-modes. The detection ability for concanavalin A (Con A) demonstrats that the limit of detection of dual-modes reaches as small as 68 and 79 nM, respectively.A novel approach for the production of both amorphous and crystalline selenium nanoparticles (SeNPs) using femtosecond laser-induced plasma shock wave on the surface of Bi2Se3 topological insulators at room temperature and ambient pressure is demonstrated. The shape and size of SeNPs can be reliably controlled via the kinetic energy obtained from laser pulses, so these are applicable as active components in nanoscale applications. Importantly, the rapid, low-cost and eco-friendly synthesis strategy developed in this study could also be extendable to other systems.A novel combined laser pulses (CLPs) consisting of a millisecond (ms) pulse and an assisted nanosecond (ns) pulse train was proposed for drilling alumina ceramic. The processing efficiency and quality were well improved by spatially and temporally superposing the ms and ns laser beams. As a result, due to the multi-reflection of keyhole and ejection of melt, the temporally superposed CLPs could decrease the energy consumption of the drilling by an order of magnitude compared with the conventional ms pulse. On the other hand, the spatial distribution of the ns laser on the focal plane was elliptical due to the off-axis distortion of the optical system. However, since the reflection of the laser in the keyhole was non-uniform, the spatially superposed CLPs showed no dependence on the shape of the focused elliptical ns laser spot in terms of the drilling quality. The research results have an important guiding for improving the efficiency and quality of laser processing, especially for the alumina ceramic laser processing.We investigated the effect of coupled quantum wells to reduce electron overflow in InGaN/GaN dot-in-a-wire phosphor-free white color light-emitting diodes (white LEDs) and to improve the device performance. The light output power and external quantum efficiency (EQE) of the white LEDs with coupled quantum wells were increased and indicated that the efficiency droop was reduced. The improved output power and EQE of LEDs with the coupled quantum wells were attributed to the significant reduction of electron overflow primarily responsible for efficiency degradation through the near-surface GaN region. Compared to the commonly used AlGaN electron blocking layer between the device active region and p-GaN, the incorporation of a suitable InGaN quantum well between the n-GaN and the active region does not adversely affect the hole injection process. Moreover, the electron transport to the device active region can be further controlled by optimizing the thickness and bandgap energy of this InGaN quantum well. In addition, a blue-emitting InGaN quantum well is incorporated between the quantum dot active region and the p-GaN, wherein electrons escaping from the device active region can recombine with holes and contribute to white-light emission.